Nutrition Innovation Centre for Food and Health, University of Ulster, Coleraine, Northern Ireland, UK.
Environmental and Biochemical Sciences Department, The James Hutton Institute, Invergowrie, Dundee, Scotland, UK.
Redox Biol. 2021 Apr;40:101862. doi: 10.1016/j.redox.2021.101862. Epub 2021 Jan 12.
Diets rich in fruit and vegetables are associated with a decreased incidence of colorectal cancer (CRC) due, in part, to the bioactive (poly)phenolic components and their microbiota-mediated metabolites. This study investigated how such compounds, derived from ingested raspberries in the gastrointestinal tract, may exert protective effects by reducing DNA damage. Ileal fluids collected pre- and post-consumption of 300 g of raspberries by ileostomists (n = 11) were subjected to 24 h ex vivo fermentation with fecal inoculum to simulate interaction with colonic microbiota. The impact of fermentation on (poly)phenolics in ileal fluid was determined and the bioactivity of ileal fluids pre- and post fermentation investigated. (Poly)phenolic compounds including sanguiin H-6, sanguiin H-10 and cyanidin-3-O-sophoroside decreased significantly during fermentation while, in contrast, microbial catabolites, including 3-(3'-hydroxyphenyl)propanoic acid, 3-hydroxybenzoic acid and benzoic acid increased significantly. The post-raspberry ileal fermentate from 9 of the 11 ileostomates significantly decreased DNA damage (~30%) in the CCD 841 CoN normal cell line using an oxidative challenge COMET assay. The raspberry ileal fermentates also modulated gene expression of the nuclear factor 2-antioxidant responsive element (Nrf2-ARE) pathway involved in oxidative stress cytoprotection, namely Nrf2, NAD(P)H dehydrogenase, quinone-1 and heme oxygenase-1. Four of the phenolic catabolites were assessed individually, each significantly reducing DNA damage from an oxidative challenge over a physiologically relevant 10-100 μM range. They also induced a differential pattern of expression of key genes in the Nrf2-ARE pathway in CCD 841 CoN cells. The study indicates that the colon-available raspberry (poly)phenols and their microbial-derived catabolites may play a role in protection against CRC in vivo.
富含水果和蔬菜的饮食与结直肠癌（CRC）的发病率降低有关，部分原因是生物活性（多）酚类成分及其微生物群介导的代谢物。本研究调查了这些化合物如何通过减少 DNA 损伤来发挥保护作用，这些化合物源自摄入胃肠道中的覆盆子。通过回肠造口术患者（n=11）在摄入 300 克覆盆子前后收集的回肠液，用粪便接种物进行 24 小时离体发酵，以模拟与结肠微生物群的相互作用。确定了发酵对回肠液中（多）酚类化合物的影响，并研究了发酵前后回肠液的生物活性。在发酵过程中，（多）酚类化合物，包括 sanguiin H-6、sanguiin H-10 和矢车菊素-3-O-槐糖苷显著减少，而相反，微生物代谢产物，包括 3-(3'-羟基苯基）丙酸、3-羟基苯甲酸和苯甲酸显著增加。在 11 个回肠造口术患者中的 9 个，用氧化应激彗星试验（COMET assay）检测到来自覆盆子回肠发酵物的 CCD 841 CoN 正常细胞系中的 DNA 损伤显著降低（~30%）。覆盆子回肠发酵物还调节了核因子 2-抗氧化反应元件（Nrf2-ARE）途径的基因表达，该途径涉及氧化应激细胞保护，即 Nrf2、NAD(P)H 脱氢酶、醌-1 和血红素加氧酶-1。评估了 4 种酚类代谢产物，它们在生理相关的 10-100 μM 范围内，每种都能显著降低氧化应激的 DNA 损伤。它们还诱导了 CCD 841 CoN 细胞中 Nrf2-ARE 途径中关键基因的不同表达模式。该研究表明，结肠可利用的覆盆子（多）酚类化合物及其微生物衍生的代谢物可能在体内预防 CRC 中发挥作用。
